The human Paramyxoviruses are important human pathogens, and are a common cause of respiratory disease in children. Approximately half of the cases of infantile bronchiolitis, croup, and pneumonia are caused by parainfluenza viruses and respiratory syncytial viruses. Although measles and mumps used to be a significant problem worldwide, their incidence has decreased greatly in developed nations due to the success of immunization campaigns, although measles remains to be a major cause of death among malnourished infants in the developing world.
Human respiratory Syncytial virus (RSV) is the main cause of lower respiratory tract infections among infants and young children. Globally, 65 million infections occur every year resulting in 160,000 deaths (Robbins, A., and Freeman, P. (1988) Sci. Am. 259, 126-133). In the United States alone, 100,000 children may require hospitalization for pneumonia and bronchiolitis caused by RSV in a single year (Glezen, W. P., Taber, L. H., Frank, A. L. and Kasel, J. A. (1986) Am. J. Dis. Child. 140, 143-146; Katz, S. L. New vaccine development establishing priorities. Vol. 1. Washington: National Academic Press. (1985) pp. 397-409). Providing inpatient and ambulatory care for children with RSV infections costs in excess of $340 million annually in the USA (Wertz, G. W., Sullender, W. M. (1992) Biotech. 20, 151-176). Severe lower respiratory tract disease due to RSV infection predominantly occurs in infants two to six months of age. Approximately 4,000 infants in the United States die each year from complications arising from severe respiratory tract disease caused by infection with RSV and Parainfluenza type 3 virus (PIV-3). The World Health Organization (WHO) and the National Institute of Allergy and Infectious Disease (NIAID) vaccine advisory committees have ranked RSV second only to HIV for vaccine development. RSV is highly infectious, and is transmitted by respiratory secretions. Although it typically presents as a febrile rhinitis and/or pharyngitis and commonly involves the inner ear, RSV results in severe illness in about 1% of all babies. Severe RSV infection is characterized by a pronounced cough and wheezing, which eventually develops into dyspnea and a high respiratory rate and hypoxemia. Additionally, pregnant women, young children, the elderly and immunosuppressed organ transplant patients are at risk for developing pneumonia due to RSV infection. Among the major challenges for RSV vaccine development include the young age of onset of serious disease, the failure of natural immunity to protect against reinfection, and the legacy of vaccine-enhanced disease.
As described above, Paramyxoviral infection, and specifically RSV infection, are prevalent throughout the population, and pose a particular risk in certain vulnerable subpopulations. Thus, there remains a need in the art for the development of an effective vaccine to treat human Paramyxovirus, and specifically RSV.